Dataset Information

Herpes Simplex Virus 1 UL2 Inhibits the TNF-?-Mediated NF-?B Activity by Interacting With p65/p50.

ABSTRACT: Herpes simplex virus 1 (HSV-1) is a large double-stranded DNA virus that encodes at least 80 viral proteins, many of which are involved in the virus-host interaction and are beneficial to the viral survival and reproduction. However, the biological functions of some HSV-1-encoded proteins are not fully understood. Nuclear factor ?B (NF-?B) activation is the major antiviral innate response, which can be triggered by various signals induced by cellular receptors from different pathways. Here, we demonstrated that HSV-1 UL2 protein could antagonize the tumor necrosis factor ? (TNF-?)-mediated NF-?B activation. Co-immunoprecipitation assays showed that UL2 could interact with the NF-?B subunits p65 and p50, which also revealed the region of amino acids 9 to 17 of UL2 could suppress the NF-?B activation and interact with p65 and p50, and UL2 bound to the immunoglobulin-like plexin transcription factor functional domain of p65. However, UL2 did not affect the formation of p65/p50 dimerization and their nuclear localizations. Yet, UL2 was demonstrated to inhibit the NF-?B activity by attenuating TNF-?-induced p65 phosphorylation at Ser536 and therefore decreasing the expression of downstream inflammatory chemokine interleukin 8. Taken together, the attenuation of NF-?B activation by UL2 may contribute to the escape of host's antiviral innate immunity for HSV-1 during its infection.

SUBMITTER: Cai M

PROVIDER: S-EPMC7237644 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Herpes Simplex Virus 1 UL2 Inhibits the TNF-α-Mediated NF-κB Activity by Interacting With p65/p50.

Cai Mingsheng M Liao Zongmin Z Zou Xingmei X Xu Zuo Z Wang Yuanfang Y Li Tong T Li Yiwen Y Ou Xiaowen X Deng Yangxi Y Guo Yingjie Y Peng Tao T Li Meili M

Frontiers in immunology 20200513

Herpes simplex virus 1 (HSV-1) is a large double-stranded DNA virus that encodes at least 80 viral proteins, many of which are involved in the virus-host interaction and are beneficial to the viral survival and reproduction. However, the biological functions of some HSV-1-encoded proteins are not fully understood. Nuclear factor κB (NF-κB) activation is the major antiviral innate response, which can be triggered by various signals induced by cellular receptors from different pathways. Here, we d ...[more]

PMID: 32477319

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Project description:VP26 is a herpes simplex virus 1 (HSV-1) small capsomere-interacting protein. In this study, we investigated the function of VP26 in HSV-1-infected cells with the following results. (i) The VP26 null mutation significantly impaired incorporation of minor capsid protein UL25 into nucleocapsids (type C capsids) in the nucleus. (ii) The VP26 mutation caused improper localization of UL25 in discrete punctate domains containing multiple capsid proteins (e.g., the VP5 major capsid protein) in the nucleus; these domains corresponded to capsid aggregates. (iii) The VP26 mutation significantly impaired packaging of replicated viral DNA genomes into capsids but had no effect on viral DNA concatemer cleavage. (iv) The VP26 mutation reduced the frequency of type C capsids, which contain viral DNA but not scaffolding proteins, and produced an accumulation of type A capsids, which lack both viral DNA and scaffold proteins, and had no effect on accumulation of type B capsids, which lack viral DNA but retain cleaved scaffold proteins. Collectively, these results indicated that VP26 was required for efficient viral DNA packaging and proper localization of nuclear capsids. The phenotype of the VP26 null mutation was similar to that reported previously of the UL25 null mutation and of UL25 mutations that preclude UL25 binding to capsids. Thus, VP26 appeared to regulate nucleocapsid maturation by promoting incorporation of UL25 into capsids, which is likely to be required for proper capsid nuclear localization.IMPORTANCE HSV-1 VP26 has been reported to be important for viral replication and virulence in cell cultures and/or mouse models. However, little is known about the function of VP26 during HSV-1 replication, in particular, in viral nucleocapsid maturation although HSV-1 nucleocapsids are estimated to contain 900 copies of VP26. In this study, we present data suggesting that VP26 promoted packaging of HSV-1 DNA genomes into capsids by regulating incorporation of capsid protein UL25 into capsids, which was reported to increase stability of the capsid structure. We also showed that VP26 was required for proper localization of capsids in the infected cell nucleus. This is the first report showing that HSV-1 VP26 is a regulator for nucleocapsid maturation.

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Dataset Information

Herpes Simplex Virus 1 UL2 Inhibits the TNF-?-Mediated NF-?B Activity by Interacting With p65/p50.

Publications

Herpes Simplex Virus 1 UL2 Inhibits the TNF-α-Mediated NF-κB Activity by Interacting With p65/p50.

Similar Datasets

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